Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: Results from the TODAY clinical trial.
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ABSTRACT:
SUBMITTER: Weinstock RS
PROVIDER: S-EPMC4482791 | biostudies-literature | 2015 Jul
REPOSITORIES: biostudies-literature
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Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: Results from the TODAY clinical trial.
Weinstock Ruth S RS Drews Kimberly L KL Caprio Sonia S Leibel Natasha I NI McKay Siripoom Vudhipoom SV Zeitler Philip S PS
Obesity (Silver Spring, Md.) 20150605 7
<h4>Objective</h4>To examine the prevalence of metabolic syndrome (MetS) in youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.<h4>Methods</h4>Prevalence of MetS (ATP III definition) was compared at baseline (n = 679) and at 6 (n = 625) and 24 months (n = 545) using chi-square tests. Laboratory data were examined between MetS classifications at each time point using ANOVA.<h4>Results</h4>Baseline prevalence of MetS was 75.8% and did no ...[more]
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Project description:ObjectiveTo determine whether self-monitoring of blood glucose (SMBG) is associated with lower HbA1c in youth with type 2 diabetes taking oral medications only or after starting insulin for persistently elevated HbA1c.Research design and methodsTreatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study participants (n = 699) taking oral medications were asked to perform SMBG twice daily. After reaching primary outcome (PO) (HbA1c ≥8% [64 mmol/mol]) over 6 months or an inability to wean from temporary insulin because of metabolic decompensation), insulin glargine was started. HbA1c and percent of SMBG (SMBG%) (percent days when the meter was used one or more times) before and after PO were analyzed.ResultsSMBG declined over time and was inversely related to HbA1c (P < 0.0001). Of 298 youth who reached PO and started insulin, 282 had SMBG data. At PO, mean ± SD age was 15.8 ± 2.3 years, BMI 35.5 ± 7.9 kg/m2, and HbA1c 9.6 ± 2.0% (81 ± 21.9 mmol/mol); 65.3% were female. Median SMBG% was 40% at PO, which increased to 49% after 6 months and fell to 41% after 1 year on insulin. At PO, 22% of youth checked ≥80% of days, which increased to 25% and fell to 19% after 6 and 12 months using insulin, respectively. At PO, compared with those who checked <80%, youth who checked ≥80% were younger and with a lower BMI, HbA1c, and blood pressure. SMBG ≥80% was associated with ≥1% reduction in HbA1c at 6 and 12 months after insulin initiation.ConclusionsLow SMBG adherence was common and associated with higher HbA1c. Optimal SMBG frequency in youth using or not using insulin, and whether less frequent SMBG is a marker for overall worse self-care, require further study.
| S-EPMC6489117 | biostudies-literature
Project description:Type 2 diabetes mellitus is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared with adults and is associated with high rates of early microalbuminuria, hypertension, and dyslipidemia. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was the first multiethnic, multicenter randomized trial in the United States to compare 3 treatment approaches in obese youth with new-onset type 2 diabetes (n=699; ages 10-17 years): monotherapy with metformin, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention. The primary outcome was glycemic control. Diabetes-related complications and cardiovascular risk factors were also examined. Approximately half of the participants could not maintain glycemic control by using metformin alone. Combination therapy with metformin and rosiglitazone resulted in better durability of glycemic control, and metformin plus intensive lifestyle intervention was intermediate but not superior to metformin alone. Deterioration in glycemic control was associated with rapid loss of beta cell function, not worsened insulin sensitivity, and could not be explained by differences in adherence or body mass index. After 3.9 years, 236 (33.8%) of participants had hypertension and 116 participants (16.6%) had microalbuminuria. Only 55.9% of participants had a low-density lipoprotein cholesterol level less than 100 mg/dL (to convert to mmol/L, multiply by 0.0259) after 3 years, and 71 of 517 participants (13.7%) had retinopathy. The significance of the findings from this important trial for the management of youth and young adults with youth-onset type 2 diabetes and its complications is discussed. An aggressive multifaceted approach is needed to prevent or forestall premature microvascular and macrovascular complications in youth-onset type 2 diabetes.
| S-EPMC4319667 | biostudies-literature
Project description:Conducting longitudinal research related to chronic illness in adolescents is inherently challenging due to developmental changes and psychosocial stressors. Participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial were socioeconomically disadvantaged as well. This study assessed attitudes and beliefs about retention in Treatment Options for type 2 Diabetes in Adolescents and Youth to shed light on the factors that potentially promote and detract from the likelihood of sustained participation.After an average 7.3?years of follow-up (range 4.9-9.5), Treatment Options for type 2 Diabetes in Adolescents and Youth participants completed a survey examining their perceptions of the benefits and barriers to sustained involvement in the protocol.The most common reasons for staying in Treatment Options for type 2 Diabetes in Adolescents and Youth included having a strong relationship with the medical team, getting study-provided diabetes care, access to free diabetes medicine and supplies, and being part of a large study to learn more about how to care for youth-onset type 2 diabetes. The most commonly endorsed challenges included scheduling conflicts, possibly disappointing others, difficulties getting to study visits, and the occurrence of other medical issues.Similar to other published reports, a supportive relationship with study staff was commonly endorsed as a benefit of engagement in the longitudinal study, suggesting that rapport, staff consistency, and relationship quality are important components of optimal retention. Moreover, our findings suggest the value of trying to remove logistical barriers, such as transportation and scheduling challenges, in order to promote long-term participation in research. Further research is recommended to evaluate factors that contribute to attrition versus retention in an a priori manner within longitudinal studies, especially protocols involving cohorts that are more vulnerable to attrition due to developmental transitions and/or socioeconomic challenges. Additional efforts to optimize quantitative and qualitative measurement of barriers would also help to expand our understanding of how to optimally retain participants in longitudinal protocols.
| S-EPMC4785072 | biostudies-literature
Project description:Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO).Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ? 8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2-6.5 years.Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies.The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.
| S-EPMC3661822 | biostudies-literature
Project description:OBJECTIVES:To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. STUDY DESIGN:TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-?, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. RESULTS:Elevated concentrations of brain natriuretic peptide (?100?pg/mL), TNF-? (?5.6?pg/mL) and troponin (?0.01?ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P?<?.05): higher left ventricular mass (39.3?±?9.0?g/m2.7), left atrial internal dimension (3.7?±?0.4?cm) and E/Em ratio, a measure of diastolic dysfunction (6.2?±?1.9). After adjustment for body mass index, these relationships were no longer significant. CONCLUSIONS:Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. TRIAL REGISTRATION:ClinicalTrials.govNCT00081328.
| S-EPMC5806514 | biostudies-literature
Project description:BackgroundThe Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy.ObjectivesWe examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms.MethodsThe 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11-17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time.ResultsLifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months.ConclusionsAlthough adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.
| S-EPMC5209292 | biostudies-literature
Project description:ObjectiveTo assess pregnancy outcomes in young women with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.Research design and methodsPregnancy information (outcome and any maternal or fetal complications) was obtained from the female participants by self-report. Additionally, medical records for the pregnancy and the child's neonatal course were obtained with data abstracted into standardized forms.ResultsOver a maximum of 15 years, 260 pregnancies were reported by 141 women (aged 21.5 ± 3.2 years, BMI 35.6 ± 7.2 kg/m2, and diabetes duration 8.1 ± 3.2 years). Contraception use prior to pregnancy was reported by 13.5% of the women. Complications were reported by 65% of the women during their pregnancy. Pregnancy loss was observed in 25.3% and preterm birth in 32.6% of pregnancies. HbA1c ≥8% was observed in 31.9% of the pregnancies, and 35% of the pregnancies were complicated by chronic hypertension. Nephropathy prior to pregnancy was observed in 25% of the women. In the offspring, 7.8% were classified as small for gestational age, 26.8% large for gestational age, and 17.9% in the macrosomic range.ConclusionsBased on observations from the TODAY cohort, young women with pregestational, youth-onset type 2 diabetes had very high rates of maternal complications stemming from significant socioeconomic disadvantage. The substantial maternal and infant complications seen in these young moms could potentially be avoided with improved contraception rates and reproductive planning.
| S-EPMC9174960 | biostudies-literature
Project description:In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the β-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered β-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue β-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.
| S-EPMC10047215 | biostudies-literature
Project description:BackgroundHigher arterial stiffness may contribute to future alterations in left ventricular systolic and diastolic function. We tested this hypothesis in individuals with youth-onset type 2 diabetes from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.MethodsArterial stiffness (pulse wave velocity [carotid-femoral, femoral-foot, and carotid-radial], augmentation index, brachial distensibility) was measured in 388 participants with type 2 diabetes (mean age, 21 years; diabetes duration, 7.7 ± 1.5 years). To reflect overall (composite) vascular stiffness, the five arterial stiffness measures were aggregated. An echocardiogram was performed in the same cohort 2 years later. Linear regression models assessed whether composite arterial stiffness was associated with left ventricular mass index or systolic and diastolic function, independent of age, sex, race/ethnicity, current cigarette smoking, and long-term exposure (time-weighted mean values over 9.1 years) of hemoglobin A1c, blood pressure, and body mass index. Interactions among arterial stiffness and time-weighted mean hemoglobin A1c, blood pressure, and body mass were also examined.ResultsAfter adjustment, arterial stiffness remained significantly associated with left ventricular mass index and diastolic function measured by mitral valve E/Em, despite attenuation by time-weighted mean body mass index. A significant interaction revealed a greater adverse effect of composite arterial stiffness on mitral valve E/Em among participants with higher levels of blood pressure over time. Arterial stiffness was unrelated to left ventricular systolic function.ConclusionsThe association of higher arterial stiffness with future left ventricular diastolic dysfunction suggests the path to future heart failure may begin early in life in this setting of youth-onset type 2 diabetes.Trial registrationClinicalTrials.gov NCT00081328.
| S-EPMC9177714 | biostudies-literature
Project description:ObjectiveThis study examined parental factors associated with outcomes of youth in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial.Research design and methodsOf 699 youth with type 2 diabetes in the TODAY cohort, 623 (89.1%) had a parent participate and provide data at baseline, including weight, HbA1c, blood pressure, symptoms of depression, binge eating (BE), and medical history. Youth were followed 2-6.5 years. Data were analyzed using regression models and survival curve methods.ResultsParental diabetes (43.6% of parents) was associated with higher baseline HbA1c (P < 0.0001) and failure of youths to maintain glycemic control on study treatment (53.6% vs. 38.2% failure rate among those without a diabetic parent, P = 0.0002). Parental hypertension (40.6% of parents) was associated with hypertension in youth during TODAY (40.4% vs. 27.4% of youth with and without parental hypertension had hypertension, P = 0.0008) and with higher youth baseline BMI z scores (P = 0.0038). Parents had a mean baseline BMI of 33.6 kg/m(2). Parental obesity (BMI >30 kg/m(2)) was associated with higher baseline BMI z scores in the youth (P < 0.0001). Depressive symptoms in parents (20.6% of parents) were related to youth depressive symptoms at baseline only (P = 0.0430); subclinical BE in parents was related to the presence of subclinical BE (P = 0.0354) and depressive symptoms (P = 0.0326) in youth throughout the study period.ConclusionsParental diabetes and hypertension were associated with lack of glycemic control, hypertension, and higher BMI z scores in youth. Further research is needed to better understand and address parental biological and behavioral factors to improve youth health outcomes.
| S-EPMC4407755 | biostudies-literature